Approximately 5000 new cases of soft tissue sarcoma are diagnosed yearly. Because of their relatively low incidence these extremely malignant tumors which arise in extraskeletal mesenchymal derived tissues have almost assumed "orphan" status in the explosive development of monoclonal antibodies (MAbs) to carcinoma cell surface associated antigens. Our laboratory has generated a series of MAbs to sarcoma related antigens which have been useful in the diagnosis of this diverse group of tumors. Characterization of MAbs generated by lectin selection of sarcoma membrane associated antigens has improved upon this series by producing a second generation of high affinity MAbs with an improved specificity for sarcoma membrane associated glycoproteins (antigens). Our specific aims are 1) select subgroups of MAbs that show broad sarcoma specificity, sarcoma subtype specificity, and affinity for shed antigens using membrane preparations of fresh surgical tissues, cultured cells, tissue sections and biochemically characterized antigens, 2) use an immunocytochemical approach to identify whether a MAb selected on the basis of RIA has a utility in aiding pathologic diagnosis, 3) expand upon the immunocytochemical approach and use selected MAbs to examine cytoxicity in vitro and in athymic mice with conjugates to a model drug an toxin. Our long term goal continues to be to secure antibodies that will improve our understanding of mesenchymal cell transformation and have a significant clinical impact in the pathological diagnosis, clinical diagnosis and therapy of soft tissue sarcoma(s).